The Health Care Systems Research Network (HCSRN)-Older Americans Independence Centers (OAICs) AGING (Advancing Geriatrics Infrastructure and Network Growth) Initiative, funded under an R24 grant mechanism (R24 AG045050), was initiated in 2014 to foster collaborations between HCSRN and OAIC (aka Pepper Centers) investigators in order to advance an interdisciplinary research agenda focused on advancing the science of multiple chronic conditions (MCCs) in older adults. The AGING Initiative is a highly productive, collaborative, transdisciplinary endeavor involving scientists from 18 HCSRN research centers, embedded within healthcare delivery systems caring for nearly 2 million persons aged 65 and older, in partnership with investigators from 15 premier, university-based centers established by the National Institute on Aging (the OAICs). Under the R24, efforts relevant to advancing MCCs science have centered around: (1) characterizing and sharing unique data resources; (2) supporting innovative, collaborative pilot projects; (3) mentoring new and early-stage investigators; and (4) disseminating research methods and findings. This collaboration has identified several understudied, high priority research domains, as well as an urgent need for formal career development support for new and early-stage scientists committed to aging research on etiology, prevention, and treatment, relevant to the care of older persons with MCCs. The overarching aim of our expanded R33 program, conceived and developed by the R24 HCSRN-OAICs AGING Initiative Steering Committee, and its Workgroups and External Advisory Committee, is to elaborate on the successful programs and infrastructure of the R24, while taking our AGING Initiative in new, more ambitious directions. We will create new core resources, career development opportunities, and funding opportunities, aligning patients' interests with those of scientists. Our specific aims are: (1) to expand on and further develop innovative methods related to measurement and analytics, observational research, and pragmatic clinical trial design and implementation, to inform the development and testing of novel interventions that improve the care and outcomes of older persons with MCCs; (2) to foster the career development and success of new and early-stage investigators, including underrepresented minorities, and create a nation-wide cohort of MCCs scholars, who are prepared to establish productive collaborations early in their careers to catalyze an expansion of interdisciplinary research relevant to the science of MCCs; (3) to create a new core function as part of an elaborated infrastructure that promotes patient-centered research by engaging patients and care partners in all stages of the research process; and (4) to fund a series of ?P-2-R? (?Pilot-to-R award?) grants that will advance the R33 research priorities relevant to the science of MCCs. The ?P-2-R? grants will serve to promote the development and implementation of larger, multi-disciplinary, multi-site studies laying a foundation upon which to continue to grow the AGING Initiative.